INTRODUCTION
As of July, 2021, there have been more than 182 million cases of COVID-19 caused by the novel SARS-CoV-2 reported worldwide, leading to nearly 4 million deaths.1-3 Recently, due to extraordinary vaccine development efforts, the American Food and Drug Administration issued Emergency Use Authorizations (EUA) for three vaccines.4-6 Despite the advent of these vaccines, effective treatments are still a target for research and development efforts, with several therapies having been granted EUA.7 Furthermore, the risk of patients with inflammatory skin diseases to develop more symptomatic COVID-19 infection is unknown, particularly in context of immunomodulatory medications.
Previous research has shown that abnormally elevated Th2 cytokines may inhibit appropriate Th1 immune responses in the setting of viral exposure, impeding the reliance on Th1 signaling in initial responses to viral infections.8-11 This is especially relevant for atopic dermatitis (AD), a disease characterized primarily by Th2 skewing,12 with an increased susceptibility to viral infections.10 Moreover, elevated expression of Th2 cytokines in serum (e.g., IL-4, IL-10, and IL-13) was reported in patients with COVID-19, especially during the cytokine storm.2,13-15
Despite the greater risk for viral infections and the baseline Th2 polarization in AD, the risk for COVID-19 incidence and symptom severity in this common disease (~7% of the adult US population),16 is still unknown. Determining COVID-19 risk profiles is particularly important in patients with moderate-to-severe AD on immunomodulatory medications. While some society guidelines recommend continuing these medications, there remains a dearth of evidence.17,18 Recent case series and studies on some inflammatory conditions suggest that immunomodulatory medications may not change the risk of infection or symptomatology.19-21 However, most of these reports were small-scale-studies or did not include AD. Furthermore, direct comparisons of COVID-19 outcomes between specific immunomodulatory drugs are lacking, making it difficult to draw conclusions about the comparative effects of different immunomodulatory medications.
Dupilumab, which inhibits the key Th2 cytokines IL-4 and IL-13, is the first FDA-approved treatment for moderate-to-severe AD, and is also approved for asthma and chronic rhinosinusitis with nasal polyps.22-24 While dupilumab has been shown to robustly modulate the Th2 pathway, it does not affect Th1 signaling.23,25 Preliminary reports have not shown increased SARS-CoV-2 infection rates among patients treated with dupilumab.26-31 However, these limited studies did not compare dupilumab-treated patients with those on other treatments or not receiving systemic treatments. To date, no study has evaluated the effects of SARS-CoV-2 exposure and infection in AD patients on dupilumab compared to other therapeutics.
The present study is the first large-scale, prospective evaluation of 1,237 patients with moderate-to-severe AD treated with dupilumab, broad immunosuppressants, or those not receiving systemic treatments. This registry study aims to investigate whether targeting type 2 inflammation with dupilumab may protect against symptomatic SARS-CoV-2 infections in patients with AD. Our data show that patients on dupilumab were less likely to develop symptomatic COVID-19 infection compared to patients on other systemic treatments for AD.